This project studies the regulation of expression of genes encoding lens fiber membrane channel proteins, which are essential for maintaining the transparency and correct refractive index of the lens. We are presently focusing on the regulation of expression of the gene encoding MIP, the major intrinsic protein of the lens fiber membrane, which is specifically expressed in the ocular lens fibers and belongs to an ancient family of transmembrane channel proteins. We have continued the study of the regulation of transcription of the MIP gene and have mapped several positive and negative cis regulatory elements in its 5'-flanking sequence. We have cloned the mouse MIP gene and found that several regulatory domains are evolutionarily conserved. Motifs containing a CT box and E box may interact with lens-specific and general transcription factors. We are characterizing the factors involved in this interaction. In collaboration with Drs. Dwight Stambolian and Jack Favor, we are characterizing the expression of the mutated MIP gene in a genetic mouse cataract, containing a mutation localized in the MIP gene locus. We found that a deletion in the exon2/intron3 junction results in the deletion of exon 2 in the resultant transcript.